The miR-424(322)/503 cluster orchestrates remodeling of the epithelium in the involuting mammary gland

The mammary gland is a very dynamic organ that undergoes continuous remodeling. The critical regulators of this process are not fully understood. Here we identify the microRNA cluster miR-424(322)/503 as an important regulator of epithelial involution after pregnancy. Through the generation of a kno...

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Detalles Bibliográficos
Autores: Llobet-Navas, David, Rodríguez-Barrueco, Ruth, Castro, Verónica, Ugalde, Alejandro P., Sumazin, Pavel, Jacob-Sendler, Damian, Demircan, Berna, Castillo Martin, Mireia, Putcha, Preeti, Marshall, Netonia, Villagrasa, Patricia, Chan, Joseph, Sanchez-Garcia, Félix, Pe'er, Dana, Rabadán, Raul, Iavarone, Antonio, Cordon Cardo, Carlos, Califano, Andrea, López-Otin, Carlos, Ezhkova, Elena, Silva, Jose M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/172282
Acceso en línea:https://hdl.handle.net/2445/172282
Access Level:acceso abierto
Palabra clave:Epiteli
Metabolisme
Expressió gènica
Glàndules mamàries
Micro RNAs
Genètica
Epithelium
Metabolism
Gene expression
Mammary glands
MicroRNAs
Genetics
Descripción
Sumario:The mammary gland is a very dynamic organ that undergoes continuous remodeling. The critical regulators of this process are not fully understood. Here we identify the microRNA cluster miR-424(322)/503 as an important regulator of epithelial involution after pregnancy. Through the generation of a knockout mouse model, we found that regression of the secretory acini of the mammary gland was compromised in the absence of miR-424(322)/503. Mechanistically, we show that miR-424(322)/503 orchestrates cell life and death decisions by targeting BCL-2 and IGF1R (insulin growth factor-1 receptor). Furthermore, we demonstrate that the expression of this microRNA cluster is regulated by TGF-β, a well-characterized regulator of mammary involution. Overall, our data suggest a model in which activation of the TGF-β pathway after weaning induces the transcription of miR-424(322)/503, which in turn down-regulates the expression of key genes. Here, we unveil a previously unknown, multilayered regulation of epithelial tissue remodeling coordinated by the microRNA cluster miR-424(322)/503.

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